Method for preparing granules or pills containing extracts in high concentration

ABSTRACT

The present invention relates to a method for preparing a granule or a pill containing a plant, medicinal herb or traditional oriental medicine decoction extract, having the steps of: (a) injecting a powdered plant, medicinal herb or traditional oriental medicine decoction extract into a fluidized-bed device and spraying purified water or a solution of the same type of extract as the extract powder at the extract powder while fluidizing the same, thereby generating microgranules of the extract powder; and (b) injecting the microgranules generated at step (a) as seeds into the fluidized-bed device and spraying a solution of the extract while fluidizing the same, thereby growing the microgranules to a predetermined size of granule or pill. According to the present invention, it is possible to prepare a granule or a pill containing an extract in a high concentration.

TECHNICAL FIELD

The present invention relates to a method for preparing granules orpills containing an extract of a plant, herbal medicine, or medicinalherb decoction in a high concentration, and granules or pills containingan extract of a plant, herbal medicine, or medicinal herb decoction in ahigh concentration, the granules or pills being prepared by the method.

BACKGROUND ART

Various kinds of extracts, that is, a plant extract, a herbal medicineextract, and a medicinal herb decoction extract, exhibit effects ofpreventing and treating various diseases and various effects helpful tothe human body, such as beauty treatment, immune enhancement, and healthpromotion. These various kinds of extracts have long been eaten, andhave been recognized as medicines with high stability due to havinglower toxicity than western medicines which are synthetic medicines, andthus have been variously researched and developed.

With this stream of times, the formulation of extracts has also beenactively researched and developed. However, there is no effectivesolution to the problem in that the contents of effective ingredients inthe formulated product of extracts are very low and thus a large doseneeds to be taken. More specifically, the herbal medicine extract andthe medicinal herb decoction extract are formulated into a liquid dosageform, a granule dosage form, or a pill dosage form, and a large dose ofliquid, granule, or pill dosage form is taken at a single dosetreatment, 2-4 times a day. Thus, a large amount of medicine needs to becarried and is in convenient to carry around, and a large dose ofmedicine needs to be frequently taken.

In addition, vegetable extracts, such as an herbal medicine extract anda medicinal herb decoction extract, are difficult to formulate into adosage form that is easy to take since the content of hydrocarbons,including sugars, such as rhamnose, arabinose, galactose, glucose,xylose, uronic acid, mannose, and galacturonic acid, is very high at45-65%. That is, the herbal medicine extract, when formulated into apowder, is difficult to handle due to severe moisture retention causedby sugars which are concentrated through the formulation into thepowder, and is problematic in long-term storage as a solid dosage formfor oral administration and in the maintenance of the stability of thedosage form, the content, and the like, due to a very high degree ofmoisture retention.

Extract powders, in particular, of Banhasihamtang, Hovenia dulcis, AlliiBulbus, Rehmanniae Radix, ginseng, and red ginseng concentrates, whichhave high contents of sugar and hydrocarbon, have a poor qualitystability at room temperature due to moisture absorption thereof, andhave a very low degree of fluidity due to the severe moisture absorptionthereof, and thus are very difficult in formulation procedures orcapsule filling procedures. In the case where other vehicles are addedto overcome the problems above, the contents of active ingredients maybe lowered more due to the addition of the additives. Thus,conventionally, various kinds of extracts need to be taken in a dosageform of a pill or powder in which the content of vehicle accounts for60-80% and the content of actual extract is 20-40%.

Meanwhile, the formulation method of an extract according to theconventional art will be described as follows. The spray drying of theextract is a physical method for making a powder. According to themethod, a powder product is produced by spraying a liquid sample assmall droplets with a size of several tens to several hundreds ofmicrometers (10-200 μm) and drying the small droplets overhigh-temperature and hot air for a drying time of 5-30 seconds. Thismethod is employed in 80% or more of pulverizing methods. However, thespray-dried powder has normal problems during the next treatmentprocedure or in the handling by a user, such as a lot of dust, poorfluidity, easy moisture absorption and oxidation, easy adherence, andpoor re-solubility. A powder having high contents of sugar andhydrocarbon, particularly, has strong moisture absorption.

A fluidized-bed device sprays a liquid-phase material toward a top orbottom space from a nozzle, which is installed at the top or bottom of afluidizing room, to generate particles having a similar shape to a driedproduct manufactured by spray-drying. At the same time, these particlesare allowed to stay in a fluidized state inside the device for apredetermined period of time, so that adhering and coating of theparticles by the liquid phase material are repeated, and thus thediameter of the particles becomes gradually increased.

With respect to the procedure for producing a product inside thefluidized-bed device, the liquid phase material is sent to the spraynozzle inside the fluidized room by a peristaltic pump, and then sprayedin a shape of a fog. The solution sprayed from the spray nozzle is driedin a droplet state, thereby generating primary particles. Thereafter,the primary particles adhere to each other by the spray liquid and thenare dried, thereby generating particles which are shaped like a bunch ofgrapes, and the generated primary particles adhere to each other by thespray liquid, thereby growing into circular granules. The grown granuleparticles repeatedly pass through the vicinity of the spray nozzle,thereby slowly increasing the particle weight and diameter. When theparticle diameter increases to some extent, the particles are highlylikely to be in contact with the spray liquid material due to the weightof the particle itself, and the spray liquid makes the particles thickersince the surface area of the particles is small. Furthermore, thecoating by surface tension for a short period of time before drying andthen the drying are repeated, and thus the growth rate of the particlesis faster. However, the fluidized-bed device can be normally operatedonly when certain content or more seeds (assembly) are allowed to stayin the device at the initial operation time to form a fluidized-bed.Various kinds of powders, such as starch, cellulose, and glucose, areused as base seeds (Korean Patent Publication No. 10-2009-0032096).However, on the other hand, these seeds function as an essentialingredient for reducing the content of active ingredient (e.g., extract)of the final product.

In this regard, Korean Patent Application Nos. 10-2007-0063355 and10-2007-0141999 disclose a method for producing granules and pills usinga fluidized-bed device adopting a lower spray manner without using baseseeds. The method is characterized in that, when an extract concentrateis sprayed in the fluidized-bed device, the extract concentrate is driedby heat, to form a powder, and the dried powder is used as a seed.However, the power producing capacity and drying efficiency of thefluidized-bed device are very poor at 15-25% even though thefluidized-bed device also has a drying function of a spray drier.

Therefore, with respect to the method for producing granules of anextract using only the fluidized-bed device without base seeds, asdescribed in the above prior patent documents, base seeds for forming aninitial fluidized bed need to be primarily formed. However, thefluidized-bed device requires a lot of time due to the low capacity toform a powder, and thus the process efficiency is very low. Since thedrying of droplets actually takes a long period of time due to the sugarand the content of sugar contained in a red ginseng concentrate, whichis sprayed in the fluidizing room at a temperature 70-85° C., thesurfaces of particles are sometimes in a wet state, and the liquid phasematerial may be coated to flow down on an inner wall of the fluidizingroom. In the case where the internal temperature of the fluidizing roomis increased to 100-150° C. to overcome the problem above, the dryingcapacity may be improved. However, the powder which is dried in a mannerdifferent from the spray drying is exposed to a high temperature for along time, and thus may be carbonized. In this regard, Koran PatentPublication No. 10-2009-0032096 discloses a method for preparingspherical granules wherein seeds of 250-750 μm grown by spraying anextract onto various seeds of 200-750 μm and base seeds of 180-250 μmare used as mother granules, and finally spherical granules of 700-1500μm containing 10-60% of seeds are produced.

Throughout this application, various patents and publications arereferenced and citations are provided in parentheses. The disclosure ofthese patents and publications in their entities are hereby incorporatedby references into this application in order to more fully describe thisinvention and the state of the art to which this invention pertains.

DETAILED DESCRIPTION OF THE INVENTION Technical Problem

The present inventors have endeavored to develop a method for preparinggranules and pills containing an extract as an active ingredient in ahigh concentration. As a result, a method for preparing granules andpills capable of containing an extract at a maximum of 100% through aseries of processes of primarily preparing microgranules of an extractpowder using a fluidized-bed device, using the prepared microgranules asbase seeds for fluidized-bed formation, and spraying an extract solutionas a binder to the prepared microgranules.

Therefore, an aspect of the present invention is to provide a method forpreparing granules or pills containing an extract of a plant, herbalmedicine, or medicinal herb decoction in a high concentration.

Another aspect of the present invention is to provide granules or pillscontaining an extract of a plant, herbal medicine, or medicinal herbdecoction in a high concentration (at a maximum of 100 wt %).

Other objects and advantages of the present invention will becomeapparent from the detailed description to follow taken in conjugationwith the appended claims and drawings.

Technical Solution

In accordance with an aspect of the present invention, there is provideda method for preparing granules or pills containing an extract of aplant, herbal medicine, or medicinal herb decoction in a highconcentration, comprising:

(a) feeding an extract powder of a plant, medicinal herb, or medicinalherb decoction into a fluidized-bed device to fluidize the extractpowder, and spraying purified water or a solution of the same kind ofextract as the extract powder onto the fluidized extract powder, therebygenerating microgranules of the extract powder; and

(b) feeding the microgranules generated in step (a) as seeds into afluidized-bed device to fluidize the microgranules, and spraying thesolution of the extract onto the microgranules, thereby growing themicrogranules into granules or pills with a predetermine size.

The present inventors have endeavored to develop a method for preparinggranules and pills containing various kinds of extracts as activeingredients in high concentrations. As a result, a method for preparinggranules and pills capable of containing an extract at a maximum of 100%through a series of processes of primarily preparing fine granules of anextract powder using a fluidized-bed device, using the preparedmicrogranules as base seeds for fluidized-bed formation, and spraying anextract solution as a binder.

Hereinafter, the method of the present invention for preparing granulesand pills containing an extract in a high concentration will bedescribed by steps as follows:

(a) Preparation of Microgranules of Extract Powder

In the present step, microgranules of an extract powder of a plant,herbal medicine, or medicinal herb decoction are prepared. Morespecifically, a extract powder of a plant, herbal medicine, or medicinalherb decoction is fed into a fluidized-bed device and fluidized, andpurified water or a solution of the same kind of extract as the extractpowder is sprayed onto the extract powder, thereby micro-granulating theextract powder.

As used herein, the term “extract” refers to a substance separated froma liquid or solid mixture by an extraction method which is normallyknown in the art. In step (a), the extract powder is used.

In step (a), the extract powder may be purchased or may be directlyprepared. Therefore, the present invention may further include a step ofpreparing the extract powder before step (a).

According to a preferable embodiment of the present invention, theextract powder may be prepared by a drying method which is normallyknown in the art, e.g., hot-air drying, freeze-drying, or naturaldrying.

According to a more preferable embodiment of the present invention, theextract powder may be prepared by using a spray dryer. The preparationof the extract powder using the spray dryer may be performed under theconditions of an inlet temperature of 145-165° C., an outlet temperatureof 75-85° C., and an extract spray rate of 500-1000 ml/h, but is notlimited thereto.

As used herein, the term “herbal medicine” refers to a natural productthat is used as a medicine, as it is, or used as a raw material ofpharmaceuticals, and includes (i) medicinal herbs of plants, or (ii)roots, barks, flowers, fruits, seeds, or horns.

In the present invention, the herbal medicine includes Puerariae Radix,Puerariae Flos, Chrysanthemi Flos, Euphorbiae Kansui Radix, EuryalisSemen, Glycyrrhizae Radix, Notopterygii Rhizoma, Zingiberis Rhizoma,Castaneae Semen, Euryales Semen, Platycodi Radix, Sinapis Semen, CassiaeSemen, Galli Stomachichum Corium, Cinnamomi Ramulus, Cinnamomi CortexSpissus, Ligustici Sinense Radix, Sophorae Radix, Oryzae FructusGerminiatus, Laminariae Thallus, Pogostemonis Herba, TrichosanthisSemen, Sophorae Flos, Fagopyri Semen, Lycii Fructus, ChrysanthemiZawadskii Herba, Chinemydis Plastrum, Lumbricus Corpus, ChrysanthemiFlos, Lonicerae Flos, Raphani Semen, Phragmitis Rhizoma, Cervi Cornu,Cervi Pantotrichum Cornu, Aloe, Rhapontici Radix, Salviae MiltiorrhizaeRadix, Angelicae gigantis Radix, Codonopsis pilosulae Radix, HordeiSemen, Arecae Pericarpium, Rhei Radix et Rhizoma, Illicii Fructus,Euphorbiae Pekinensis Radix, Allii Bulbus, Zizyphi Folium, PersicaeSemen, Angelicae Pubescentis Radix, Beninecasae Semen, Malvae Semen,Cordyceps, Eucommiae Cortex, Junci Medulla, Cannabis Fructus, Mate,Hirudonis Caro, Viticis Fructus, Hordei Fructus Germiniatus, LiriopesRadix, Gossypii Semen, Chaenomelis Fructus, Ostreae Concha, MoutanCortex, Akebiae Caulis, Aucklandiae Radix, Myrrha, Menthae Herba,Pinelliae Rhizoma, Stephaniae tetrandrae Radix, Ledebouriellae Radix,Bombyx Batryticatus, Amomi Rotundus, Amomi Rotundus Fructus, BiotaeSemen, Thujae Resina, Atractylodis Rhizoma Alba, Trionycis Carapax,Psoraleae Fructus, Atractylodis Rhizoma, Rubi Fructus, ZedoariaeRhizoma, Eriobotryae Folium, Arecae Semen, Adenophorae Radix, CnidiiFructus, Amomi Fructus, Croci Flos, Crataegii Fructus, Corni Fructus,Dioscoreae Rhizoma, Zizyphi Spinosae Semen, Zanthoxyli Pericarpium,Scirpi Rhizoma, Taxilli Ramulus, Mori Cortex, Mori Folium, MantidisOotheca, Phellini Polyporus, Zingiberis Rhizoma Recens, HaliotidisConcha, Dendrobii Herba, Acori Graminei Rhizoma, Asari herba cum Radice,Cardamomi Fructus, Sappan Lignum, Perillae Fructus, Dipsaci Radix, PiniPollen, Cynomorii Herba, Cimicifugae Rhizoma, Bupleuri Radix, MassaMedicata Fermentata, Magnoliae Fios, Asini Gelatinum, AgaricusPolyporus, Alpiniae Officinarum Rhizoma, Artemisiae argi Folium,Ligustri Lucidi Fructus, Nelumbinis Semen, Forsythiae Fructus, RosaeFructus, Ganodermae Polyporus, Acanthopanacis Cortex, ScolopendraCorpus, Aconiti Ciliare Tuber, Trogopterorum Faeces, Mume Fructus,Schizandrae Fructus, Evodiae Fructus, Linderae Radix, Otariae Testis etPenis, Orostachyos Herba, Fossilia ossis Mastodi, Borneol, GentianaeRadix, Bovis Fel, Arctii Fructus, Achyranthis Bidentatae Radix, CoriolusPolyporus, Curcumae Radix, Polygalae Radix, Clematidis Radix, PolygonatiOdorati Rhizoma, Ulmi Cortex, Olibanum, Myristicae Semen, CistanchesHerba, Coicis Semen, Epimedii Herba, Alpiniae oxyphyllae Fructus,Lonicerae Caulis, Ginseng Radix, Artemisiae Capillaris Herba, PterocarpiLignum, Perillae Folium, Asteris Radix, Hominis Placenta, PaeoniaeRadix, Bombycis Excrementum, Jasmin, Polyporus, Scorpio, PeucedaniRadix, Bambusae caulis in Taeniam, Phyllostachys Folium, CaryophylliFlos, Houttuyniae Herba, Aurantii Fructus, Lycii Radicis Cortex, HoveniaSemen, Anemarrhenae Rhizoma, Aurantii immaturus Fructus, SanguisorbaeRadix, Rehmanniae Radix (Rehmanniae Radix et Rhizoma Preparata,Rehmanniae Radix Siccus, Rehmanniae Radix Preparat), Fraxini Cortex,Tribuli Fructus, Theae Folium, Plantaginis Semen, Xanthii Fructus,Atractylodis Rhizoma, Arisaematis Rhizoma, Cnidii Rhizoma, GastrodiaeRhizoma, Asparagi Radix, Zanthoxyli Pericarpium, Citrii Unshiu ImmaturiPericarpium, Alpiniae katsumadai Semen, Biotae Cacumen, Aquilariaeresinatum Lignum, Gardeniae Fructus, Matricaria chamomilla Linne,Coffee,Alismatis Rhizoma, Cuscutae Semen, Morindae Radix, Crotonis Fructus,Fritillariae Ussuriensis Bulbus, Taraxci Herba, Aconiti TuberPraepareta, Agaricus Polyporus, Prunellae Spica, Polygoni multifloriRadix, Notarchi Leachii Ovum, Erythrinae Cortex, Eucheumae Thallus,Armeniacae Semen, Cyperi Rhizoma, Elsholtziae Herba, ScrophulariaeRadix, Corydalidis Tuber, Nepetae Herba, Scutellariae Radix, AstragaliRadix, Phellodendri Cortex, Coptidis Rhizoma, Polygonati Rhizoma, HumuliFlos, red ginseng, Carthami Flos, Magnogliae Cortex, Pireris NigriFructus, Siegesbeckiae Herba, Foeniculi Fructus, Glycinis Semen Nigra,and Pharbitidis Semen, but is not limited thereto.

As used herein, the term “medicinal herb decoction” refers to anindividual medicine composition by medicinal herbs standardmanufacturing process instructions or prescriptions, and includesSipjeondaebotang, Gamikwibitang, Gamiondanmtang, Sosihotang, Sihamtang,Ongyeongtang, Yukgunjatang, Yijungtang, Cheongseoikgitang,Banhasihamtang, Saenggangsasimtang, Ganghwaryupungtang, Kwibitang,Siryeongtang, and Sihogyejitang, but is not limited thereto.

As used herein, the term “plant” refers to one excluding animals fromliving organisms constituting a biology system, and more specifically,refers to living organisms that have cell walls and chlorophyll and thusare photosynthetic. The plants included are pine needles, Taraxacumplatycarpum, mulberry leaves, Codonopsis lanceolata, Rosa multiflora,Artemisia capillaries, Platycodon grandiflorum, Rubus coreanus Miguel,Artemisia princeps Pamp., Lonicera japonica Thunberg, Adenophoratriphylla var. japonica, and Hovenia dulcis, but are not limitedthereto.

Herein, the binder is sprayed onto the seeds (powder type extract) toform microgranules of a corresponding extract powder through repetitivecoating and drying, or and/or form microgranules by binding the extractpowder and the extract powder to each other.

According to a preferable embodiment of the present invention, thebinder is purified water or a solution of the extract (liquid phaseextract), and preferably is a solution of the same type of extract asthe extract powder. The content of extract in the microgranule can beraised when the solution of the extract is used as the binder ratherthan when the purified water is used as the binder.

In step (a) of the present invention, the binder may be sprayed from thetop in a top-spray manner, or the bottom in a bottom-spray manner in thefluidized-bed device, and preferably may be sprayed from the top in atop-spray manner in the fluidized-bed device. When the binder solutionis sprayed during the fluidizing of the powder, powder particles areliquid cross-linked to each other, and then moisture is evaporated,thereby forming aggregates each composed of three or four powderparticles through solid cross-linking. Thereafter, micro-powderparticles are continuously linked to each other, thereby forming, socalled, raspberry-shaped granules. With respect to the top-spray manner,while a powder moves from the bottom to the top, the binder solution issprayed downwards from the top in a movement direction of the powder,thereby increasing the frictional force between a droplet and amicroparticle caused by increases in the movements of droplets andmicroparticles in opposite directions and/or the contact frequencybetween particles, and thus the top-spray manner has a much higherpossibility of forming liquid cross-linkage between microparticles thanthe bottom-spray manner.

In the following examples, microgranules of Acanthopanax senticosus,Astragalus membranaceus, Banhasihamtang, Sipjeondaebotang,Cheongseoikgitang, Rehmanniae Radix Preparat, Angelica gigas and Alliumvictorialis, Hovenia dulcis, and red ginseng were prepared by sprayingextract solutions from the top in a fluidized-bed device in thetop-spray manner.

In step (a), the flowing rate of the binder, the nozzle pressure, thehot-air temperature, and the air volume can be controlled inconsideration of the viscosity, adhesive strength, and droplet moistureevaporation rate of the liquid material which is sprayed onto thebinder. That is, since a liquid material having high viscosity andadhesive strength is easy to become amorphous, the binder is preferablycontrolled to have a slow flowing rate or be appropriately diluted.Particularly, as for the purified water, the cross-linking force formingfunction of instantly dissolving and then linking micro powder particlesis lost at a high-air temperature and a large air volume since themoisture evaporation is easy, and thus the microgranules are difficultto form. In step (a) of the present invention, the flowing rate of thebinder, nozzle pressure, hot-air temperature, and air volume for formingmicrogranules of the extract powder can be easily determined by a personskilled in the art.

According to a preferable embodiment of the present invention, in thecase where the purified water as the binder is sprayed to preparemicrogranules, the temperature of the fluidizing room is 70-75° C., thefeeding rate of the extract is 100-250 ml/h, and the spray pressure is0.5 kg/cm² at an initial state and then may be increased to a range of0.5-5.0 kg/cm² while observing the fluidized state. In the case wherethe extract solution as the binder is sprayed to prepare microgranules,the temperature of the fluidizing room is 65-70° C., the feeding rate ofthe extract is 100-200 ml/h, and the spray pressure is 0.5 kg/cm² at aninitial state and may be increase to a range of 0.5-5.0 kg/cm² whileobserving the fluidized state.

According to step (a) of the present invention, various sizes ofmicrogranules can be prepared, and the diameter of the microgranulesgenerated in step (a) of the present invention is 500 μm or less,preferably 300 μm or less, more preferably 200 μm or less, still morepreferably 150 μm or less, still more preferably 1-150 μm, still morepreferably 10-150 μm, still more preferably 20-150 μm, still morepreferably 30-150 μm, still more preferably 40-150 μm, still morepreferably 50-150 μm, still more preferably 60-150 μm, still morepreferably 70-150 μm, still more preferably 80-150 μm, still morepreferably 90-150 μm; still more preferably 1-120 μm, still morepreferably 10-120 μm, still more preferably 20-120 μm, still morepreferably 30-120 μm, still more preferably 40-120 μm, still morepreferably 50-120 μm, still more preferably 60-120 μm, still morepreferably 70-120 μm, still more preferably 80-120 μm, still morepreferably 90-120 μm.

Meanwhile, the microgranules generated in step (a) of the presentinvention may be prepared into tablets through tableting. Here, avehicle, a coating agent, a lubricant, and/or a disintegrating agent maybe used as an additive for preparing tablets to control the moldingcapability, fluidity, and disintegrability of the microgranules, and canbe made into an enteric type highly functional preparation.

Plant type extract powders are impossible to tablet due to moistureabsorptivity thereof, but the microgranules generated in step (a) can beused for tableting. Preferably, in the case where the microgranulesgenerated in step (a) are used for tableting, the microgranules arecoated with the moisture-proofing coating agent in a content of 1-2%based on the amount of the raw material, and then may be used fortableting.

(b) Preparation of Granules and Pills

In the present step, the microgranules generated in step (a) are fed asseeds for fluidized-bed formation and fluidized, and a liquid phaseextract is sprayed to grow the microgranules into granules or pills witha desired size.

A feature of the present invention is to obtain microgranules of theextract-dried powder using a fluidized-bed device, and to feed theobtained microgranules as seeds for fluidized-bed formation, therebypreparing granules and pills. In the case where the microgranules areused as seeds for fluidized-bed formation, the microgranules are highlylikely to be in contact with the sprayed liquid material (binder) thanthe extract powder, and are more thickly coated with the spray liquidthan the extract powder due to a small surface area thereof, therebyquickening the growth of the particle diameter by adhering or coating.

According to a preferable embodiment of the present invention, in step(b) of the present invention, the temperature of the fluidizing room is65-70° C., the feeding rate of the extract is 120-200 ml/h, and thespray pressure is 0.7 kg/cm² at an initial state and may be increase toa range of 1.0-3.0 kg/cm² depending on the fluidized state.

According to step (b) of the present invention, granules and pills witha desired size can be prepared. In step (b) of the present invention,the prepared granules has a diameter of preferably 1-3 mm, and theprepared pills has a diameter of preferably 4-10 mm, more preferably 4-9mm, and still more preferably 4-8 mm.

In step (b) of the present invention, the extract solution as the bindermay be sprayed from the top in a top-spray manner, or the bottom in abottom-spray manner in the fluidized-bed device, and may preferably besprayed from the bottom in a bottom-spray manner in the fluidized-beddevice. The bottom-spray manner is easier in increasing the size ofpills and has a higher efficiency of moisture removal and thus achievingmore uniform drying than the top-spray manner, and thus can produce moreuniform spherical-shaped produce granules and pills without irregularaggregation between particles. In the following examples, granules witha diameter of 2-3 mm and pills with a size of 8 mm were prepared byspraying the extract solution from the bottom in a bottom-spray mannerin a fluidized-bed device.

According to a preferable embodiment of the present invention, steps (a)and (b) may be sequentially performed in the same fluidized-bed deviceequipped with both a top-spray system and a bottom-spray system.

The present invention can preferably produce granules and pills in thesame fluidized-bed device through a series of processes of step (a) ofgenerating microgranules in a top-spray manner and step (b) of feedingthe generated microgranules as seeds and then spraying a binder from thebottom in a bottom-spray manner.

(c-1) Preparation of Granules and Pills Using Rotor

The present invention may further include: a powder layering step (c-1)of directly binding the microgranule particles of step (a) to surfacesof the granule particles of step (b) via a liquid phase extract using afluidized-bed device provided with a rotor, after step (b). Morespecifically, in step (c-1), the granules generated in step (b) are fedas seeds into the rotor of the fluidized-bed device and fluidized, andthe extract solution is sprayed to the fluidized granules while themicrogranules generated in step (a) are transferred into the rotor,thereby obtaining granules or pills growing to a desired size.

That is, another feature of the present invention is to prepare granulesand pills more promptly by feeding the granules generated in step (b) asbase seeds into a rotor of a fluidized-bed device equipped with arotating disk and rotation-fluidizing the granules, feeding themicrogranules generated in step (a) from a feeder while the rotor isrotated, and spraying the extract solution as a binder.

According to step (c-1) of the present invention, the sizes of thegranules and pills can be increased more promptly and the granules andpills can have a more uniform size when compared with those in step (b).

According to a preferable embodiment of the present invention, themicrogranules supplied into the rotor may be coated with a coating agentbefore being supplied. That is, the microgranules are coated with acoating agent but do not adhere to each other only while themicrogranules are transferred into the rotor, and then supplied into therotor.

A usable coating agent includes ethyl cellulose, methyl cellulose,hydroxypropyl cellulose, polyvinyl pyrrolidone, polyethylene, aquateric,Eudragit™, acrylic coatings, Surelease™, and cellulose acetatephthalate, but is not limited thereto.

Preferably, the microgranules may be coated with ethyl cellulose. Thatis, the microgranules may be coated with ethyl cellulose of 1-2% basedon the weight of the microgranules but do not adhere to each other onlywhile the microgranules are transferred into the rotor, and thensupplied into the rotor.

According to a preferable embodiment of the present invention, step(c-1) of the present invention may be performed under the conditionswhere the rotation rate of the rotating disk is 50-1000 rpm, andpreferably 200-800 rpm; the set temperature of the fluidized-bed deviceis 20-90° C.; the temperature in the rotor is 25-70° C.; the spray rateof the extract solution is 100-500 ml/h; and the spray pressure is0.5-3.0 kg/cm², and preferably conditions where the rotation rate of therotation disk is 250-450 rpm; the temperature of the rotating room ofthe rotor in the fluidized-bed device is 25-45° C.; and the spray rateof the extract solution is 10 g/min. When the particle size grows withthe lapse of time, the rotation rate of the rotating disk, thetemperature of the rotating room of the rotor, and the spray pressure ofthe solvent are gradually increased, thereby controlling the rotatingand mixing of rotating particles to be smoothened.

According to a preferable embodiment of the present invention,microgranules with a diameter of 100 μm or less (product in step (a))and granules with a diameter of 1-3 mm (product in step (b)) maybe usedin step (c-1).

According to step (c-1) of the present invention, granules and pillswith desired sizes can be prepared, and more preferably, the granulesand pills prepared in step (c-1) of the present invention have diametersof 1-3 mm and 4-8 mm, respectively.

According to a preferable embodiment of the present invention, steps(a), (b), and (c-1) may be sequentially performed in that order in thesame fluidized-bed device equipped with both a top-spray system, abottom-spray system, and a tangential rotor system.

(C-2) Coating

The present invention may further include, after step (b), coatingsurfaces of the granules or pills generated in step (b) with amoisture-proofing material (c-2).

In step (c-2) of the present invention, one of various kinds ofmoisture-proofing coating materials known in the art may be selected andused.

The moisture-proofing coating material includes starch, gelatin, naturalfood colors, artificial food colors, cellulose, biodegradable polymers,biodegradable oligomers, emulsifying wax, shellac, flavoring agents,hydrophobizing agents or hydrophilizing agents, lipids, proteins, andminerals. Preferably, the moisture-proofing coating material may be atleast one selected from the group consisting of hydroxypropylmethylcellulose, hydroxypropyl cellulose, ethyl cellulose, methylcellulose, titanium dioxide, polyethylene glycol, triethyl citrate,triacetin, dibutyl sebacate, polymethacrylate, cellulose acetatephthalate, carnauba wax, candelila was, petroleum wax, beeswax, and palmoil, but is not limited thereto.

The surfaces of the granules and pills prepared in step (b) or (c-1) ofthe present invention are coated with a water-proofing coating material,thereby improving stability on storage and stability in the distributionprocess.

In accordance with another aspect of the present invention, there isprovided granules or pills containing an extract of a plant, herbalmedicine, or medicinal herb decoction, the granules or pills beingprepared by the method of the present invention, wherein the extract iscontained in up to 100 wt % with respect to the granule or pill.

Since the granules or pills containing an extract of a plant, herbalmedicine, or medicinal herb decoction of the present invention areprepared by the above described method of the present invention,descriptions of overlapping contents therebetween will be omitted toavoid excessive complication of the specification due to repetitivedescriptions thereof.

The granules or pills containing an extract of a plant, herbal medicine,or medicinal herb decoction, which are prepared by the method of thepresent invention, contain an extract as an active ingredient exhibitinga medicinal effect, in a high concentration of 80-100 wt %, preferably90-100 wt %, and more preferably 98-100 wt %. Therefore, the granulesand pills of the present invention can overcome problems of theconventional granules and pills in that a large dose needs to befrequently taken, and thus is inconvenient to carry about since a largeamount of medicine needs to be carried. Therefore, the granules andpills of the present invention can be maximally utilized as functionalhealth food, herbal medicines, and various basic processed products.

Advantageous Effects

Features and advantages of the present invention are summarized asfollows:

(i) The present invention can produce microgranules and pills with adesired size through processes of primarily obtaining microgranules ofan extract dried powder by feeding the extract dried powder as a seedinto a fluidized-bed device and then spraying a binder thereonto, andthen using the microgranules as base seeds for fluidized-bed formationand spraying a binder thereonto.

(ii) The present invention can produce microgranules and pills with adesired size through a series of processes of spraying a binder in atop-spray manner in the step of preparing microgranules, and sprayingthe binder in a bottom-spray manner in the step of preparing granulesand pills.

(iii) The present invention can produce microgranules and pills with adesired size through processes of feeding granules as seeds into a rotorof a fluidized-bed device and spraying a liquid phase extract while themicrogranules are transferred into the rotor.

(iv) According to the present invention, granules and pills containingan extract in a high concentration (at a maximum of 100 wt %).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically illustrates a whole flow chart showing a preparingmethod of the present invention.

FIG. 2 shows actual images of granules and pills prepared by processesin example 3. (a) Sipjeondaebotang granules; (b) Red ginseng concentratepills; and (c) Acanthopanax senticosus granules

FIG. 3 shows an actual image of Sipjeondaebotang pills prepared by aprocess in example 4. Dark regions indicate granules with a diameter of3 mm in the image.

FIG. 4 shows images of final products produced according to thepreparing method of the present invention. {circle around (1)}Acanthopanax senticosus; {circle around (2)} Astragalus membranaceus;{circle around (3)} Banhasihamtang; {circle around (4)}Sipjeondaebotang; {circle around (5)} Cheongseoikgitang (rectangularpreparation: coated with green color); {circle around (6)} Rehmanniaglutinosa (Circular and rectangular preparations); {circle around (7)}Angelica gigas+Allium victorialis (rectangular preparation); {circlearound (8)} Hovenia dulcis; and {circle around (9)} red ginseng.

MODE FOR CARRYING OUT THE INVENTION

The present invention will now be described in further detail byexamples. It would be obvious to those skilled in the art that theseexamples are intended to be more concretely illustrative and the scopeof the present invention as set forth in the appended claims is notlimited to or by the examples.

EXAMPLES Example 1 Preparation of Extract Powder Through Spray Drying

In the present example, Acanthopanax senticosus, Astragali Radix,Angelicae gigantis Radix and Allii Bulbus, Hovenia dulcis, and six-yearold red ginseng were used as sources for herbal medicine extractsamples. For medicinal herb decoctions, decoctions composed of less than10 species, 10 species, and more than 10 species of raw materials wereselected, and corresponding standard decoctions were Banhasihamtang(Pinelliae Rhizoma, Scutellariae Radix, Zingiberis Rhizoma, AdenophoraeRadix, Glycyrrhizae Radix, Jujubae Fructus, and Coptidis Rhizoma; sevenspecies), Sipjeondaebotang (Jujubae Fructus, Cinnamomi Ramulus,Angelicae gigantis Radix, Adenophorae Radix, Paeoniae Radix Alba,Astragali Radix, Cnidii Rhizoma, Rehmanniae Radix Preparat, AtractylodisRhizoma, and Atractylodis macrocephalae Rhizoma; 10 species); andCheongseoikgitang (Puerariae Radix, Jujubae Fructus, Angelicae gigantisRadix, Liriopis Tuber, Adenophorae Radix, Atractylodis macrocephalaeRhizoma, Cimicifugae Rhizoma, Massa Medicata Fermentata, PhellodendriCortex, Astragali Radix, Alismatis Rhizoma, Citri reticulatae viridePericarpium, Atractylodis Rhizoma, Fraxini Cortex, and SchizandraeFructus: 15 species).

{circle around (1)} Preparation of Acanthopanax senticosus Powder

5 kg of Acanthopanax senticosus and 50 kg of purified water were fedinto a herbal extractor, allowed to steep for 2 hours at roomtemperature, and then extracted for 3 hours at 95° C., followed byfiltration. The extract was spray-dried using a spray dryer (SD-1000,Eyela) having an inlet temperature of 150° C., an outlet temperature of85° C., and an extract spray rate of 500 ml/h. Approximately 900 g ofdried powder was prepared per batch of the extract.

{circle around (2)} Preparation of Astragali Radix Powder

5 kg of Astragali Radix and 50 kg of purified water were fed into anherbal extractor, allowed to steep for 2 hours at room temperature, andthen extracted for 3 hours at 95° C., followed by filtration. Theextract was spray-dried using a spray dryer (SD-1000, Eyela) having aninlet temperature of 160° C., an outlet temperature of 95° C., and anextract spray rate of 1000 ml/h. Approximately 500 g of dried powder wasprepared per batch of the extract.

{circle around (3)} Preparation of Banhasihamtang Powder

5 kg of Banhasihamtang prescription raw materials, which were preparedby an oriental medicine clinic, and 50 kg of purified water were fedinto a herbal extractor, allowed to steep for 2 hours at roomtemperature, and then extracted for hours at 95° C., followed byfiltration. The extract was spray-dried using a spray dryer (SD-1000,Eyela) having an inlet temperature of 145° C., an outlet temperature of80° C., and an extract spray rate of 800 ml/h. Approximately 1,050 g ofdried powder was prepared per batch of the extract.

{circle around (4)} Preparation of Sipjeondaebotang Powder

5 kg of Sipjeondaebotang prescription raw materials, which were preparedby an oriental medicine clinic, and 50 kg of purified water were fedinto a herbal extractor, allowed to steep for 2 hours at roomtemperature, and then extracted for hours at 95° C., followed byfiltration. The extract was spray-dried using a spray dryer (SD-1000,Eyela) having an inlet temperature of 145° C., an outlet temperature of80° C., and an extract spray rate of 800 ml/h. Approximately 1,250 g ofdried powder was prepared per batch of the extract.

{circle around (5)} Preparation of Cheongseoikgitang Powder

5 kg of Cheongseoikgitang prescription raw materials, which wereprepared by an oriental medicine clinic, and 50 kg of purified waterwere fed into a herbal extractor, allowed to steep for 2 hours at roomtemperature, and then extracted for 3 hours at 95° C., followed byfiltration. The extract was spray-dried using a spray dryer (SD-1000,Eyela) having an inlet temperature of 145° C., an outlet temperature of80° C., and an extract spray rate of 800 ml/h. Approximately 950 g ofdried powder was prepared per batch of the extract.

{circle around (5)} Preparation of Rehmanniae Radix Preparat Powder

5 kg of Rehmanniae Radix Preparat which was purchased from a herbalmedicine shop and 50 kg of purified water were fed into a herbalextractor, allowed to steep for 2 hours at room temperature, and thenextracted for 3 hours at 95° C., followed by filtration. The extract wasspray-dried using a spray dryer (SD-1000, Eyela) having an inlettemperature of 145° C., an outlet temperature of 80° C., and an extractspray rate of 700 ml/h. Approximately 2,250 g of dried powder wasprepared per batch of the extract.

{circle around (7)} Preparation of Angelicae gigantis Radix and AlliiBulbus Powder

5 kg of Angelicae gigantis Radix and Allii Bulbus, which are mixed at aratio of 20:80 based on a weight ratio obtained by converting themoisture content of a raw material into 10%, and 50 kg of purified waterwere fed into a herbal extractor, allowed to steep for 2 hours at roomtemperature, and then extracted for 3 hours at 95° C., followed byfiltration. The extract was spray-dried using a spray dryer (SD-1000,Eyela) having an inlet temperature of 145° C., an outlet temperature of80° C., and an extract spray rate of 800 ml/h. Approximately 2,050 g ofdried powder was prepared per batch of the extract.

{circle around (8)} Preparation of Hovenia dulcis Powder

5 kg of Hovenia dulcis and dried fruits thereof and 50 kg of purifiedwater were fed into a herbal extractor, allowed to steep for 2 hours atroom temperature, and then extracted for hours at 95° C., followed byfiltration. The extract was spray-dried using a spray dryer (SD-1000,Eyela) having an inlet temperature of 145° C., an outlet temperature of80° C., and an extract spray rate of 800 ml/h. Approximately 1,350 g ofdried powder was prepared per batch of the extract.

{circle around (9)} Preparation of Red Ginseng Powder

5 kg of 6-year old red ginseng and 50 kg of purified water were fed intoa herbal extractor, allowed to steep for 2 hours at room temperature,and then extracted for 3 hours at 95° C., followed by filtration. Theextract was spray-dried using a spray dryer (SD-1000, Eyela) having aninlet temperature of 145° C., an outlet temperature of 80° C., and anextract spray rate of 800 ml/h. Approximately 2,600 g of dried powderwas prepared per batch of the extract.

Example 2 Preparation of Microgranules in Top-Spray Manner byFluidized-Bed Device

Microgranules were prepared from each of the dried powders prepared inexample 1 using a top-spray system of a fluidized-bed device (FBGC-3,Chungjin Tech Korea) provided with the top-spray system, a bottom-spraysystem, and a tangential rotor system. When the microgranules wereprepared in a top spray manner, an extract corresponding to each of thedried powders or purified water was used as a binder. When the extractwas used, the fluidizing room temperature was set to 65-70° C., theextract feeding rate to 150-200 ml/h, and the spray pressure to 1kg/cm², and the spray pressure was increased to a range of 1.5-3.5kg/cm² while observing the fluidized state. When the purified water wasused, the fluidizing room temperature was set to 70-75° C., the extractfeeding rate to 180-250 ml/h, and the spray pressure to 1 kg/cm², andthe spray pressure was increased to a range of 1.5-3.5 kg/cm² whileobserving the fluidized state. In addition, when the extract was used,600-1000 g of the corresponding dried powder was fed as a base seed, andwhen the purified water was used, 1200-1500 g of the corresponding driedpowder was fed. For a binder, 1500 g of the corresponding extract wassprayed, and 2000 g of purified water was sprayed in the Banhasihamtang,Angelicae gigantis Radix and Allii Bulbus, and Hovenia dulcis. Theresults of preparing microgranules by the methods were tabulated intable 1. Samples coated with shellac or ethyl cellulose, shown in table1, were prepared for tableting in example 5 below, and the sizes ofgranules and pills were measured after additional processes in theexamples below.

TABLE 1 Results of preparing microgranules in top-spray manner and finalproducts thereof Top-spray process Average Comparison Base Microgranuleparticle (final Sample Seed production size product No. Sample Name (g)Binder (g) (g) (μm) content %) {circle around (1)} Acanthopanax 600Corresponding 900 100 Up to 4 mm- senticosus extract 1500 sized granules(100%) {circle around (2)} Astragali Radix 1000 Corresponding 1150 100Up to 2.3 mm- extract 1500 sized granules (100%) {circle around (3)}Banhasihamtang 1500 Purified 1470 80 Up to 2.3 mm- water 2000 sizedgranules (100%) {circle around (4)} Sipjeondaebotang 1000 Corresponding1370 100 Up to 8 mm- extract 1500 sized pills (98.52%) {circle around(5)} Cheongseoikgitang 800 Corresponding 1080 100 Coated extract 1500with 1% shellac and then tableted (86.36%) {circle around (6)}Rehmanniae Radix 1000 Corresponding 1650 100 Coated Preparat extract1500 with 1% ethyle cellulose and then tableted (98%) {circle around(7)} Angelicae 1500 Purified 1480 80 Coated gigantis Radix water 2000with 2% and Allii Bulbus ethyle cellulose and then tableted (85%){circle around (8)} Hovenia dulcis 1200 Purified 1170 80 2 mm-sizedwater 2000 granules containing capsule (100%) {circle around (9)}Six-year old red 1000 Corresponding 1750 100 2 mm-sized ginseng extract1500 granules and 8 mm- sized pills (100%)

Example 3 Preparation of Granules and Pills in Bottom-Spray Manner byFluidized-Bed Device

The microgranules prepared in example 2 above were fed as base seeds forfluidized-bed formation into the bottom-spray system of thefluidized-bed device (FBGC-3, Chungjin Tech Korea), thereby preparingcircular granules and pills. More specifically, 1000 g of microgranulesof each of Astragali Radix, Banhasihamtang, and Hovenia dulcis preparedin example 2 above were fed as base seeds for fluidized-bed formation.The fluidizing room temperature was set to 65-70° C., and the extractfeeding rate was increased from 120 ml/h to 200 ml/h. The spray pressurewas gradually increased from 1 kg/cm² at an initial state to a range of1.5-2.0 kg/cm² while observing the fluidized state. Also, 750 g ofmicrogranules of each of Acanthopanax senticosus, Sipjeondaebotang, andred ginseng were fed as base seeds for fluidized-bed formation, to growthe particle size to 3-4 mm. For Sipjeondaebotang and red ginseng, thisprocedure was repeated one more time, and the spray pressure wasincreased to 5 kg/cm² at the maximum limit. In the present process, inorder to increase the growing rate of the particle size, the initialsolid content (concentration of 5-20%) of the corresponding extract wasconcentrated to 30-40%. Through this process, Astragali Radix,Banhasihamtang, and Hovenia dulcis pills were prepared to have adiameter of 2.3 mm, Acanthopanax senticosus and Sipjeondaebotang pillswere prepared to have a diameter of 3-4 mm, and Sipjeondaebotang and redginseng pills were prepared to have a diameter of 8 mm (FIG. 2).

Example 4 Preparation of Granules and Pills Using Rotor System ofFluidized-Bed Device

In the preparation of pills using a tangential rotor system of afluidized-bed device (FBGC-3, Chungjin Tech Korea), Sipjeondaebotanggranules with a diameter of about 3 mm prepared in example 3 were used.With respect to the powder constantly fed into the inside of the rotorfrom the outside, the microgranules prepared in example 2, which wascoated with a 1.5% solution in which ethyl cellulose corresponding to 2%based on 1500 g of the microgranules was dissolved in ethyl alcohol,were fed into the rotor at a constant rate using a feeder. That is, 500g of the granules with a size (diameter) of 3 mm, which was previouslyprepared in example 3, were fed as seeds into a fluidized-bed rotorsystem provided with a rotating circular disk, and then the microgranulepowder coated with ethyl cellulose was fed into a granulator at a rateof 10 g/min while the rotor system is rotated at 250 rpm. While theinternal temperature of the rotor is maintained at 25° C., aSipjeondaebotang extract prepared in example 1 was sprayed as a binderat a rate of 10 ml/min, thereby growing the microgranules into pillswith a size of 8 mm. FIG. 3 shows an image of Sipjeondaebotang pillsthat have been prepared, and it can be confirmed from FIG. 3 that themicrogranule powder is coated in layers on the surface of theSipjeondaebotang granule with a size of 3 mm (FIG. 3).

Example 5 Preparation of Circular and Rectangular Tablets UsingTableting Machine

In the last step of the micro-granulating procedure in example 2, thedried powder of each of Cheongseoikgitang, Rehmanniae Radix Preparat,and Angelicae gigantis Radix and Allii Bulbus was surface-coated with ashellac or ethyl cellulose solution, thereby allowing the powder to haveimproved fluidity in a tableting procedure. Then, raw materials shown intable 2 below were mixed to prepare rectangular and circular tablets.Models KISAN KP-410 and KISAN KF-S50 were used for a tableting machineand a capsule filling machine, respectively. As shown in FIG. 4, it wasconfirmed that the fluidity was favorable without tangle (cementation)of powder raw materials mixed before tableting, and there were noproblems in the moldability for being manufactured into products,binding force, and stability after being manufactured into products.

TABLE 2 Mixing ratio of raw materials for tableting (%) AngelicaeRehmanniae gigantis Radix + Raw material Cheongseoikgitang Radix AlliiBulbus Microgranule 95 98 85 powder Avi-cell 2.5 1.0 5.0 Saccharose- 0.50.5 2.0 fatty acid ester stearic acid — — 5.0 magnesium HPMC 2.0 0.5 3.0total, % 100 100 100 Note Coated with — — gardenia green^(a) Finalcontent 86.36% 98% 85% (%) ^(a)The tablet was externally coated with a5% solution in which, based on 100 g of a tablet, 5.5% TiO₂, 2.5%hydroxypropyl methylcellulose (HPMC), and 2.0% gardenia green aredissolved in 70% ethyl alcohol was prepared, using a sugar coated tabletcoater.

Having described a preferred embodiment of the present invention, it isto be understood that variants and modifications thereof falling withinthe spirit of the invention may become apparent to those skilled in thisart, and the scope of this invention is to be determined by appendedclaims and their equivalents.

1.-10. (canceled)
 11. Granules or pills containing an extract of aplant, herbal medicine, or medicinal herb decoction, which are preparedby a method comprising: (a) feeding an extract powder of a plant,medicinal herb, or medicinal herb decoction into a fluidized-bed deviceto fluidize the extract powder, and spraying purified water onto thefluidized extract powder, thereby generating micro granules of theextract powder, the microgranules having a diameter of 1-150 μm; and (b)feeding the microgranules generated in step (a) as seeds into afluidized-bed device to fluidize the microgranules, and spraying asolution of the same kind of extract as the extract powder onto themicrogranules, thereby growing the microgranules into granules having adiameter of 1-3 mm or pills having a diameter of 4-10 mm, wherein theextract is contained in up to 100 wt % with respect to the granule orpill.
 12. The granules or pills of claim 11 wherein the method furthercomprising, before step (a), preparing the extract powder of a plant,medicinal herb, or medicinal herb decoction in a spray dryer.
 13. Thegranules or pills of claim 11, wherein in step (a), the purified wateris sprayed from the top of the fluidized-bed device in a top-spraymanner.
 14. The granules or pills of claim 13, wherein in step (b), thesolution of the extract is sprayed from the bottom of the fluidized-beddevice in a bottom-spray manner.
 15. The granules or pills of claim 11,wherein the method further comprising: (c-1), after step (b), feedingthe granules generated in step (b) as seeds into a rotor of afluidized-bed device to fluidize the granules, and spraying the solutionof the extract onto the fluidized granules while the microgranulesgenerated in step (a) are transferred into the rotor, thereby obtaininggranules or pills growing to a predetermined size.
 16. The granules orpills of claim 11, wherein the method further comprising: (c-2), afterstep (b), surface-coating the granules or pills generated in step (b)with a moisture-proofing material.
 17. The granules or pills of claim16, wherein the moisture-proofing material is selected from the groupconsisting of hydroxypropyl methylcellulose, hydroxypropyl cellulose,ethyl cellulose, methyl cellulose, titanium dioxide, polyethyleneglycol, triethyl citrate, triacetin, dibutyl sebacate, polymethacrylate,cellulose acetate phthalate, carnauba wax, candelila wax, petroleum wax,beeswax, and palm oil.